- Volume 13 Issue 8
Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, and the role of the MTHFR C677T polymorphism in pancreatic carcinogenesis is still controversial. Methods: A literature search was performed using Pubmed and CNKI databases for published studies through May 2012. We performed a meta-analysis of all relevant case-control studies that examined the association between MTHFR C677T polymorphism and pancreatic cancer risk. Results: Finally, 9 individual case-control studies with a total of 1,299 pancreatic cancer cases and 2,473 controls were included into this meta-analysis. Results: This metaanalysis showed there was an obvious association between MTHFR C677T polymorphism and pancreatic cancer risk in East Asians (for allele model, OR = 1.67, 95%CI 1.11-2.51; For homozygote model, OR = 2.77, 95%CI 1.40-5.48; for recessive model, OR = 1.96, 95%CI 1.54-2.50; for dominant model, OR = 2.11, 95%CI 1.01-4.41). However, no significant association was found in Caucasians. Conclusions: The MTHFR C677T polymorphism is associated with pancreatic cancer risk, and a race-specific effect may exist in this association. More studies with a larger sample size are needed to further clarify this association.
Methylenetetrahydrofolate reductase;genetic polymorphism;pancreatic cancer;meta-analysis
- Chiou WK, Huang BY, Chou WY, et al (2011). Incidences of cancers in diabetic and non-diabetic hospitalized adult patients in Taiwan. Asian Pac J Cancer Prev, 12, 1577-81.
- Cochran WG (1954). The combination of estimates from different experiments. Biometrics, 10, 101-29. https://doi.org/10.2307/3001666
- Crider KS, Yang TP, Berry RJ, et al (2012). Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate's role. Adv Nutr, 3, 21-38. https://doi.org/10.3945/an.111.000992
- DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7, 177-88. https://doi.org/10.1016/0197-2456(86)90046-2
- Dong LM, Potter JD, White E, et al (2008). Genetic susceptibility to cancer: the role of polymorphisms in candidate genes. JAMA, 299, 2423-36. https://doi.org/10.1001/jama.299.20.2423
- Egger M, Davey Smith G, Schneider M, et al (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629-34. https://doi.org/10.1136/bmj.315.7109.629
- Frosst P, Blom HJ, Milos R, et al (1995). A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet, 10, 111-3. https://doi.org/10.1038/ng0595-111
- Goyette P, Sumner JS, Milos R, et al (1994). Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nat Genet, 7, 195-200. https://doi.org/10.1038/ng0694-195
- Goyette P, Pai A, Milos R, et al (1998). Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR). Mammalian Genome, 9, 652-6. https://doi.org/10.1007/s003359900838
- Hidalgo M (2010). Pancreatic cancer. N Engl J Med, 362, 1605-17. https://doi.org/10.1056/NEJMra0901557
- Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
- Kouidhi S, Rouissi K, Khedhiri S, et al (2011). MTHFR gene polymorphisms and bladder cancer susceptibility: a metaanalysis including race, smoking status and tumour stage. Asian Pac J Cancer Prev, 12, 2227-32.
- Li D, Ahmed M, Li Y, et al (2005). 5,10-Methylenetetrahydrofolate reductase polymorphisms and the risk of pancreatic cancer. Cancer Epidemiol Biomarkers Prev, 14, 1470-6. https://doi.org/10.1158/1055-9965.EPI-04-0894
- Lin D, Li H, Tan W, et al (2007). Genetic polymorphisms in folate- metabolizing enzymes and risk of gastroesophageal cancers: a potential nutrient-gene interaction in cancer development. Forum Nutr, 60, 140-5.
- Liu YX, Wang B, Wan MH, et al (2011). Meta-analysis of the relationship between the metholenetetrahydrofolate reductase C677T genetic polymorphism, folate intake and esophageal cancer. Asian Pac J Cancer Prev, 12, 247-52.
- Lin Y, Yagyu K, Egawa N, et al (2011). An overview of genetic polymorphisms and pancreatic cancer risk in molecular epidemiologic studies. J Epidemiol, 21, 2-12. https://doi.org/10.2188/jea.JE20100090
- Mantel N, Haenszel W (1959). Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst, 22, 719-48.
- Matsubayashi H, Skinner HG, Iacobuzio-Donahue C, et al (2005). Pancreaticobiliary cancers with deficient methylenetetrahydrofolate reductase genotypes. Clin Gastroenterol Hepatol, 3, 752-60. https://doi.org/10.1016/S1542-3565(05)00359-9
- Milne RL, Greenhalf W, Murta-Nascimento C, et al (2009). The inherited genetic component of sporadic pancreatic adenocarcinoma. Pancreatology, 9, 206-14. https://doi.org/10.1159/000210261
- Nisevic I, Dinic J, Nikolic A, et al (2008). MTHFR C677T polymorphism in chronic pancreatitis and pancreatic adenocarcinoma. Cell Biochem Funct, 26, 659-63. https://doi.org/10.1002/cbf.1487
- Raimondi S, Maisonneuve P, Lowenfels AB (2009). Epidemiology of pancreatic cancer: an overview. Nat Rev Gastroenterol Hepatol, 6, 699-708. https://doi.org/10.1038/nrgastro.2009.177
- Suzuki T, Matsuo K, Sawaki A, et al (2008). Alcohol drinking and one-carbon metabolism-related gene polymorphisms on pancreatic cancer risk. Cancer Epidemiol Biomarkers Prev, 17, 2742-7. https://doi.org/10.1158/1055-9965.EPI-08-0470
- Taghavi A, Fazeli Z, Vahedi M, et al (2011). Pancreatic cancer mortality and misclassification--bayesian analysis. Asian Pac J Cancer Prev, 12, 2271-4.
- Wang L, Lin DX, Lu XH, et al (2006). Study on the relations between genetic polymorphisms in methylenetetrahydrofolate reductase, methionine synthase and the risk of pancreatic cancer. Zhonghua Liu Xing Bing Xue Za Zhi, 27, 50-4 (in Chinese).
- Wang L, Miao X, Tan W, et al (2005). Genetic polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase and risk of pancreatic cancer. Clin Gastroenterol Hepatol, 3, 743-51. https://doi.org/10.1016/S1542-3565(05)00156-4
- Yang XO, Qian JM (2009). The study of the releVant SNPs on the risk of pancreatic cancer and high risk population. Chinese Post-Graduate Dissertations, Peking Union Medical College.
- The MTHFR C677T polymorphism and global DNA methylation in oral epithelial cells vol.36, pp.4, 2013, https://doi.org/10.1590/S1415-47572013005000035
- Significant association between GSTT1 null genotype and susceptibility to pancreatic cancer vol.40, pp.7, 2013, https://doi.org/10.1007/s11033-013-2516-4
- Folate intake and risk of bladder cancer: a meta-analysis of epidemiological studies vol.65, pp.3, 2014, https://doi.org/10.3109/09637486.2013.866641
- The methylenetetrahydrofolate reductase (MTHFR) 677 C>T polymorphism increases the risk of developing chronic myeloid leukemia—a case-control study vol.36, pp.4, 2015, https://doi.org/10.1007/s13277-014-2946-1